Drug design environment – SOMA2 The SOMA2 project 2002-2006 Tekes (National Technology Agency of Finland) DRUG2000 program. Organizes and updates CSCs (the Finnish IT Center for Science) modeling program environment to meet the standards in modern computer-aided molecular design. Promotes the use of computing tools in drug discovery research work in Finland. Provides easy access to computational tools through WWW – interface. Integrates different tools, operates as middleware program. Allows user to define unique computational workflow (pipeline, network etc.).
Software for ADME and structure-based drug discovery Databases of chemistry and protein structures and tools to analyze them Docking and classification of molecules QSAR (Quantitative Structural Analysis Research) Computer-assisted high-throughput screening Design of ligands ADME predictions (Absorption, Distribution, Metabolism and Excretion), Toxicity Data management, data mining and visualization FROM MOLECULES … … TO PROTEINS … …AND CELL-LEVEL ACTIVITIES Drug design environment – SOMA2
Query database ISIS on Solaris Calculate chemical properties Sybyl on Linux Convert to 3D Corina on Solaris Dock to target protein GOLD on Linux INTERNET, researchers PC Scientist interface, SOMA2 environment CSC-network and computing grid SOMA2 environment 2D > 3D conversion ADME prediction Docking 2D structure, 3D structure, original data, docking score, ADME-values 2D structure, known data INPUT: OUTPUT: CML XML a) b) Drug design environment – SOMA2 Basic technical concept WWW – interface is based on the XML – description of a program. Different machine architectures are hidden. Automatic generation of program and platform specific configuration files. CML (chemical markup language) is used as internal data format (data transferred in XML). Unique computational workflows.
Drug design environment – SOMA2 Model workflow Figure from: Lehtovuori, P. Nyrönen, T., SOMA - Workflow for Small Molecule Property Calculations on a Multiplatform Computing Grid, J. Chem. Inf. Model., 2006, 46(2), 620-625.
Drug design environment – SOMA2 Generic user interface generation User interface generated from description that is based on XML schema (template). No programming skills required to produce XML – description of a program. New programs are easily added to SOMA2 – environment. Save expert user knowledge in XML. Flexibility Not only for cheminformatics and drug design. SOMA2 – system can be applied in almost every application area. Open source thinking Similar products available usually they are commercial. Although some of the programs used are commercial, SOMA2 system is planned to be open source.
Drug design environment – SOMA2 Model workflows User can choose a predefined workflow for specific task. Predefined workflow can still be freely modified. Possibility to save own workflows as a template.
Drug design environment – SOMA2 Input molecules Upload files from local computer. Sketch molecules within the user interface.
Drug design environment – SOMA2 Database query MDL ISIS host databases. Support for structure search. Search results imported to SOMA2 – system or downloaded.
Drug design environment – SOMA2 Program configuration Easy configuration of programs. Useful help texts and reasonable defaults included in program XML. System includes model templates for running a program.
Drug design environment – SOMA2 Workflow manager Free navigation between steps. Insert, change and delete operation supported.
Result view Spreadsheet like result view. Tools for sorting and filtering data. Basic data analysis. Save molecular data in different formats. Drug design environment – SOMA2
Result details Visualisation of the result molecules. Summary of computed properties.
Additional information CSC – the Finnish IT Center for Science http://www.csc.fi SOMA2 – project: http://www.csc.fi/proj/drug2000/index.phtml.en Acknowledgements Tekes (National Technology Agency of Finland): http://www.tekes.fi ChemAxon Ltd.: http://www.chemaxon.com